In the mammalian kidney, the macula densa segment of the distal tubule is in close proximity with the vascular elements of its own glomerulus. The macula densa cells detect alterations in the total solute concentration of distal tubular fluid and transmit signals to the glomerular vasculature causing changes in vascular tone. Increases in luminal fluid solute concentration are associated with vasoconstriction, while decreases in solute concentration result in vasodilation. This mechanism has been termed tubulo-glomerular feedback. Using single nephron micropuncture techniques in the rat, stop flow pressure (SFP), which is an estimate of glomerular capillary pressure, is measured before and during microperfusion of the macula densa segment. In response to microperfusion with an isotonic Ringer's solution, there are feedback mediated decreases in SFP of about 30 percent. Over the last several years, my primary area of interest has been the mechanisms responsible for the transmission of feedback signals from the distal tubular fluid to the vascular smooth muscle. One important aspect of this problem is the mechanism for the detection of changes in the composition of distal tubular fluid by the macula densa cells. In preliminary studies using the calcium ionophore A23187, I have found that increases in the feedback receptor cell calcium lead to the generation of SFP feedback responses. These results suggest that alterations in receptor cell free calcium concentration may serve as the intermediary transmission step between distal tubule and glomerular vascular elements. The studies which are outlined in this proposal will more fully evaluate the role of intracellular calcium in the mediation of feedback responses. Four general problems will be addressed: first, does increases in luminal fluid total solute concentration lead to the generation of feedback responses through increases in receptor cell calcium; second, is the source for the increase in receptor cell calcium from luminal fluid or intracellular stores; third, does calcium per se, directly lead to the transmission of the signal, or does calcium exert its effects through a calcium dependent protein such as calmodulin; and four, what are some of the factors that may influence the transmission of the feedback signal by altering the level of the intracellular calcium concentration.